Lack of Early Improvement with Antipsychotics is a Marker for Subsequent Nonresponse in Behavioral and Psychological Symptoms of Dementia: Analysis of CATIE-AD Data

Kazunari Yoshida, Rachel Roberts, Takefumi Suzuki, Barry Lebowitz, Suzanne Reeves, Robert Howard, Takayuki Abe, Masaru Mimura, Hiroyuki Uchida

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objective: Prediction of response or nonresponse to antipsychotics is especially important in patients with behavioral and psychological symptoms of dementia (BPSD) in whom antipsychotic exposure increases risks of death. This study examined whether the presence or absence of early improvement of BPSD with antipsychotics is associated with subsequent response or nonresponse. Methods: In a post-hoc analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) study (2001-2004) (clinicaltrials.gov; NCT00015548) in 45 U.S. sites, 245 subjects (olanzapine, N = 90; quetiapine, N = 81; risperidone, N = 74) with a DSM-IV diagnosis of dementia of the Alzheimer type who presented with a score of 1 or more in the Brief Psychiatric Rating Scale (BPRS) at baseline (phase I of CATIE-AD) were randomly assigned to treatment with olanzapine, quetiapine, risperidone, or placebo in a double-blind manner. Associations were examined between response at week 8 and demographic and clinical characteristics, including BPRS total score reduction at week 2, using logistic regression analyses. Prediction performance of binary classification (presence or absence) of improvement or no improvement at week 2 for response at week 8 was examined. Results: BPRS total score reduction at week 2 (mean percentage score reduction: 12.6%) was significantly associated with response at week 8 (odds ratio: 1.18; 95% CI: 1.11-1.26). The 5% score reduction cut-off at week 2 showed the highest accuracy (0.71), with sensitivity, specificity, and positive and negative predictivevalues of 0.76, 0.65, 0.69, and 0.72, respectively. Conclusion: Lack of even a very small early improvement with antipsychotic treatment may be a marker of subsequent nonresponse in BPSD.

Original languageEnglish
JournalAmerican Journal of Geriatric Psychiatry
DOIs
Publication statusAccepted/In press - 2016 Sep 18

Fingerprint

Behavioral Symptoms
Antipsychotic Agents
Dementia
Alzheimer Disease
Clinical Trials
olanzapine
Psychology
Brief Psychiatric Rating Scale
Risperidone
Clinical Trials, Phase I
Diagnostic and Statistical Manual of Mental Disorders
Logistic Models
Odds Ratio
Placebos
Regression Analysis
Demography
Sensitivity and Specificity
Therapeutics

Keywords

  • Antipsychotics
  • Behavioral and psychological symptoms with dementia (BPSD)
  • CATIE-AD
  • Dementia
  • Prediction
  • Response

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Lack of Early Improvement with Antipsychotics is a Marker for Subsequent Nonresponse in Behavioral and Psychological Symptoms of Dementia : Analysis of CATIE-AD Data. / Yoshida, Kazunari; Roberts, Rachel; Suzuki, Takefumi; Lebowitz, Barry; Reeves, Suzanne; Howard, Robert; Abe, Takayuki; Mimura, Masaru; Uchida, Hiroyuki.

In: American Journal of Geriatric Psychiatry, 18.09.2016.

Research output: Contribution to journalArticle

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abstract = "Objective: Prediction of response or nonresponse to antipsychotics is especially important in patients with behavioral and psychological symptoms of dementia (BPSD) in whom antipsychotic exposure increases risks of death. This study examined whether the presence or absence of early improvement of BPSD with antipsychotics is associated with subsequent response or nonresponse. Methods: In a post-hoc analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) study (2001-2004) (clinicaltrials.gov; NCT00015548) in 45 U.S. sites, 245 subjects (olanzapine, N = 90; quetiapine, N = 81; risperidone, N = 74) with a DSM-IV diagnosis of dementia of the Alzheimer type who presented with a score of 1 or more in the Brief Psychiatric Rating Scale (BPRS) at baseline (phase I of CATIE-AD) were randomly assigned to treatment with olanzapine, quetiapine, risperidone, or placebo in a double-blind manner. Associations were examined between response at week 8 and demographic and clinical characteristics, including BPRS total score reduction at week 2, using logistic regression analyses. Prediction performance of binary classification (presence or absence) of improvement or no improvement at week 2 for response at week 8 was examined. Results: BPRS total score reduction at week 2 (mean percentage score reduction: 12.6{\%}) was significantly associated with response at week 8 (odds ratio: 1.18; 95{\%} CI: 1.11-1.26). The 5{\%} score reduction cut-off at week 2 showed the highest accuracy (0.71), with sensitivity, specificity, and positive and negative predictivevalues of 0.76, 0.65, 0.69, and 0.72, respectively. Conclusion: Lack of even a very small early improvement with antipsychotic treatment may be a marker of subsequent nonresponse in BPSD.",
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T2 - Analysis of CATIE-AD Data

AU - Yoshida, Kazunari

AU - Roberts, Rachel

AU - Suzuki, Takefumi

AU - Lebowitz, Barry

AU - Reeves, Suzanne

AU - Howard, Robert

AU - Abe, Takayuki

AU - Mimura, Masaru

AU - Uchida, Hiroyuki

PY - 2016/9/18

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N2 - Objective: Prediction of response or nonresponse to antipsychotics is especially important in patients with behavioral and psychological symptoms of dementia (BPSD) in whom antipsychotic exposure increases risks of death. This study examined whether the presence or absence of early improvement of BPSD with antipsychotics is associated with subsequent response or nonresponse. Methods: In a post-hoc analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) study (2001-2004) (clinicaltrials.gov; NCT00015548) in 45 U.S. sites, 245 subjects (olanzapine, N = 90; quetiapine, N = 81; risperidone, N = 74) with a DSM-IV diagnosis of dementia of the Alzheimer type who presented with a score of 1 or more in the Brief Psychiatric Rating Scale (BPRS) at baseline (phase I of CATIE-AD) were randomly assigned to treatment with olanzapine, quetiapine, risperidone, or placebo in a double-blind manner. Associations were examined between response at week 8 and demographic and clinical characteristics, including BPRS total score reduction at week 2, using logistic regression analyses. Prediction performance of binary classification (presence or absence) of improvement or no improvement at week 2 for response at week 8 was examined. Results: BPRS total score reduction at week 2 (mean percentage score reduction: 12.6%) was significantly associated with response at week 8 (odds ratio: 1.18; 95% CI: 1.11-1.26). The 5% score reduction cut-off at week 2 showed the highest accuracy (0.71), with sensitivity, specificity, and positive and negative predictivevalues of 0.76, 0.65, 0.69, and 0.72, respectively. Conclusion: Lack of even a very small early improvement with antipsychotic treatment may be a marker of subsequent nonresponse in BPSD.

AB - Objective: Prediction of response or nonresponse to antipsychotics is especially important in patients with behavioral and psychological symptoms of dementia (BPSD) in whom antipsychotic exposure increases risks of death. This study examined whether the presence or absence of early improvement of BPSD with antipsychotics is associated with subsequent response or nonresponse. Methods: In a post-hoc analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) study (2001-2004) (clinicaltrials.gov; NCT00015548) in 45 U.S. sites, 245 subjects (olanzapine, N = 90; quetiapine, N = 81; risperidone, N = 74) with a DSM-IV diagnosis of dementia of the Alzheimer type who presented with a score of 1 or more in the Brief Psychiatric Rating Scale (BPRS) at baseline (phase I of CATIE-AD) were randomly assigned to treatment with olanzapine, quetiapine, risperidone, or placebo in a double-blind manner. Associations were examined between response at week 8 and demographic and clinical characteristics, including BPRS total score reduction at week 2, using logistic regression analyses. Prediction performance of binary classification (presence or absence) of improvement or no improvement at week 2 for response at week 8 was examined. Results: BPRS total score reduction at week 2 (mean percentage score reduction: 12.6%) was significantly associated with response at week 8 (odds ratio: 1.18; 95% CI: 1.11-1.26). The 5% score reduction cut-off at week 2 showed the highest accuracy (0.71), with sensitivity, specificity, and positive and negative predictivevalues of 0.76, 0.65, 0.69, and 0.72, respectively. Conclusion: Lack of even a very small early improvement with antipsychotic treatment may be a marker of subsequent nonresponse in BPSD.

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KW - Behavioral and psychological symptoms with dementia (BPSD)

KW - CATIE-AD

KW - Dementia

KW - Prediction

KW - Response

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